1. Field of the Invention
The present invention relates to, for example, a method for forming an organ of mammals; especially to, for example, a method for forming a mammals' tooth root, mammals' periodontal tissues (periodontium) and a complex structure (unit) thereof.
2. Description of the Related Art
Recent interest has focused on regenerative medical techniques which aim to restore the forms (morphology) and functions of organs suffering from tissue loss or functional disorders. In this technical field, demand has arisen for provision of regenerated organs replaceable with organs suffering from, for example, functional disorders. Such regenerated organs are required to have normal morphology and functions, and also to be formed by a technique involving no in vivo culturing. This is because there is any risk that organs formed through xenotransplantation or allotransplantation are associated with immune rejection and infection with viruses.
Thus, there is a need to regenerate organs through in vitro culturing, which does not involve such infection or other problems.
For example, in dental therapy where the regeneration of a tooth is desired, the following treatment is needed rather than using tooth crowns restored with prostheses by modern clinical techniques in dentistry. Specifically, it is desired to provide a tooth root having functions of, for example, fixing a tooth in the jawbone and supporting a tooth crown; and periodontal tissues (periodontal ligament, alveolar bone, cementum and gingiva) supporting the tooth root. In particular, it is desired to provide tooth roots having periodontal ligament and alveolar bone. Periodontal ligament is a soft tissue (connective tissue) embedded between the cementum and the inner wall of the alveolar bone socket. This periodontal ligament has the functions of cushioning mechanical forces and enabling sensory perception during chewing.
Young C S, Terada S, Vacanti J P, Honda M, Bartlett J D and Yelick P C disclose a technique based on in vivo culturing in “Tissue engineering of complex tooth structures on biodegradable polymer scaffolds; J. Dent. Res, 81, 695-700, 2002.” Specifically, a cell suspension is prepared using various kinds of tooth germ-derived cells obtained from unerupted third molars of six-month-old pigs, and then applied to biodegradable polymer shaped into the form of tooth, whereby artificial tooth germs are formed. The thus-formed tooth germs are xenotransplanted into rat's omentum (intraperitoneal fat membrane) where abundant blood flows to supply a sufficient amount of nutrients and oxygen. It was confirmed that small tooth-like tissue such as enamel, dentin and dental pulp were formed 25 weeks to 30 weeks after transplantation.
Modino S A and Sharpe P T disclose a technique of reproducing the developmental processes of a tooth, focusing on epithelial-mesenchymal interactions in “Tissue engineering of teeth using adult stem cells; Arch. Oral Biol., 50, 255-258, 2005.” According to this literature, artificial tooth germs are prepared by combining tooth germ epithelium taken from mouse embryos at embryonic day 10 with, rather than tooth germ mesenchyme, three kinds of stem cells which are not derived from tooth germs. Thereafter, the thus-prepared artificial tooth germs are allotransplanted under the kidney capsule of adult mice, and grown through in vivo culturing for 12 days to form teeth.
As described in “Young C S, Terada S, Vacanti J P, Honda M, Bartlett J D, Yelick P C, Tissue engineering of complex tooth structures on biodegradable polymer scaffolds; J. Dent. Res, 81, 695-700, 2002” and “Modino S A, Sharpe P T; Tissue engineering of teeth using adult stem cells; Arch. Oral Biol., 50, 255-258, 2005,” hitherto, there are known only tooth regeneration techniques that require xenotransplantation or allotransplantation (in vivo culturing). This is because, as described in “The Journal of the Japan Dental Association, Vol. 60, No. 7, October 2007, 657-674,” in vitro culture cannot form complete teeth, and also cannot form periodontal tissues due to lack of bones such as alveolar bone. Therefore, at present, it is necessary to perform xenotransplantation or allotransplantation (in vivo culture) in order to form teeth. In addition, no report has been presented on regeneration of human teeth, and clinically, metal (titanium) is used as a dental implant (artificial tooth root) to take the place of the tooth root.